IL-1β Suppresses Innate IL-25 and IL-33 Production and Maintains Helminth Chronicity

Approximately 2 billion people currently suffer from intestinal helminth infections,which are typically chronic in nature and result in growth retardation,vitamin a deficiency,anemia and poor cognitive function. such chronicity results from co-evolution between helminths and their mammalian hosts; however,the molecular mechanisms by which these organisms avert immune rejection are not clear. we have found that the natural murine helminth,heligmosomoides polygyrus bakeri (hp) elicits the secretion of il-1β in vivo and in vitro and that this cytokine is critical for shaping a mucosal environment suited to helminth chronicity. indeed in mice deficient for il-1β (il-1β-/-),or treated with the soluble il-1βr antagonist,anakinra,helminth infection results in enhanced type 2 immunity and accelerated parasite expulsion. il-1β acts to decrease production of il-25 and il-33 at early time points following infection and parasite rejection was determined to require il-25. taken together,these data indicate that hp promotes the release of host-derived il-1β that suppresses the release of innate cytokines,resulting in suboptimal type 2 immunity and allowing pathogen chronicity. © 2013 zaiss et al.